1. Forskolin-induced swelling of intestinal organoids predicts long-term cystic fibrosis disease progression
- Author
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Zomer-van Ommen Dd, Peter van Mourik, Dompeling E, Gitte Berkers, Roukema J, de Winter-de Groot Km, Brunsveld Jb, Annelotte M. Vonk, Jans, Sylvia W.F. Suen, Sabine Michel, Weersink Ej, de Poel E, van der Ent Kk, Evelien Kruisselbrink, Marne C. Hagemeijer, Gerard H. Koppelman, Jeffrey M. Beekman, Vries R, Eijkemans Rj, van Panhuis H, H. Oppelaar, D. Muilwijk, van de Meer R, and van der Eerden Mm
- Subjects
Forskolin ,biology ,business.industry ,Disease ,medicine.disease ,Cystic fibrosis ,Cystic fibrosis transmembrane conductance regulator ,chemistry.chemical_compound ,Liver disease ,chemistry ,Diabetes mellitus ,Cancer research ,biology.protein ,Organoid ,Biomarker (medicine) ,Medicine ,business - Abstract
Patient-derived organoids hold great potential as predictive biomarker for disease expression or therapeutic response. Here, we used intestinal organoids to estimate individual cystic fibrosis transmembrane conductance regulator (CFTR) function of people with cystic fibrosis, a monogenic life-shortening disease associated with more than 2000 CFTR mutations and highly variable disease progression. In vitro CFTR function in CF intestinal organoids of 176 individuals with diverse CFTR mutations was quantified by forskolin induced swelling and was strongly associated with longitudinal changes of lung function and development of pancreatic insufficiency, CF-related liver disease and diabetes. This association was not observed when the commonly used biomarker of CFTR function sweat chloride concentration was used. The data strongly exemplifies the value of an organoid-based biomarker in a clinical disease setting and supports the prognostic value of forskolin induced swelling of intestinal organoids, especially for people with CF who have rare CFTR genotypes with unclear clinical consequences.
- Published
- 2021